Inhibitory effect of sesquiterpene lactones and the sesquiterpene alcohol aromadendrane-4β,10α-diol on memory impairment in a mouse model of Alzheimer

Eur J Pharmacol. 2015 Dec 15:769:195-202. doi: 10.1016/j.ejphar.2015.11.018. Epub 2015 Nov 24.

Abstract

Alzheimer's disease (AD), a progressive neurodegenerative disorder of the aged brain with no known cause or cures, has become a major medical and social problem for industrialized countries. Cerebral deposition of amyloid-β peptide (Aβ) is a critical feature of AD. The use of medicinal plants as an alternative form of prevention, or even as a possible treatment of AD, is therefore interesting areas of research. Sesquiterpene lactones and a sesquiterpene alcohol are compounds found in H. brasiliense that have several anti-oxidative and anti-inflammatory effects. In the present study, we investigated whether these compounds have neuroprotective effects in an amyloid-β peptide-induced Alzheimer's disease mouse model. Mice were injected with Aβ1-42 peptide intracerebroventricularly and were subsequently injected (i.c.v.) with 1µg/site of IGM-A (15-acetoxy-isogermafurenolide), IGM-H (15-hydroxy-isogermafurenolide), PDA (Podoandin), EHP (1,2-epoxy-10α-hydroxy-podoandin), HDS (13-hydroxy-8,9-dehydroshizukanolide), and ARD (aromadendrane-4β,10α-diol). Seven days after treatments the animals had their memory tested in the inhibitory avoidance. After the behavioral testing of animals the brains were removed and subjected to biochemical tests for oxidative stress. The results showed that ARD, HDS and PDA significantly ameliorated the Aβ1-42 peptide-induced memory impairment in the passive avoidance task (P<0.05). In addition, GSH activity was increased while the TBARS levels were decreased by treatment with these compounds. These results suggest that these compounds inhibit the cognitive deficit of animals induced peptide amyloid and may be potential candidates for Alzheimer's disease therapy.

Keywords: Alzheimer; Hedyosmum brasiliense; Sesquiterpene alcohol; Sesquiterpene lactones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / complications*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Avoidance Learning / drug effects
  • Behavior, Animal / drug effects
  • Brain / drug effects
  • Brain / metabolism
  • Disease Models, Animal
  • Magnoliopsida / chemistry
  • Male
  • Maze Learning / drug effects
  • Memory Disorders / complications*
  • Memory Disorders / drug therapy*
  • Memory Disorders / metabolism
  • Memory Disorders / physiopathology
  • Mice
  • Neuroprotective Agents / chemistry*
  • Neuroprotective Agents / isolation & purification
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Oxidative Stress / drug effects
  • Peptide Fragments / metabolism
  • Plant Leaves / chemistry
  • Sesquiterpenes / chemistry*
  • Sesquiterpenes / isolation & purification
  • Sesquiterpenes / pharmacology*
  • Sesquiterpenes / therapeutic use
  • Sesquiterpenes, Guaiane

Substances

  • Amyloid beta-Peptides
  • Neuroprotective Agents
  • Peptide Fragments
  • Sesquiterpenes
  • Sesquiterpenes, Guaiane
  • amyloid beta-protein (1-42)
  • aromadendrane
  • aromadendranediol